Increased susceptibility against Cryptococcus neoformans of lupus mouse models (pristane-induction and FcGRIIb deficiency) is associated with activated macrophage, regardless of genetic background

• Published in: The journal of microbiology Vol. 57; no. 1; pp. 45 - 53
• Main Authors: Surawut, Saowapha, Makjaroen, Jiradej, Thim-uam, Arthid, Wongphoom, Jutamas, Palaga, Tanapat, Pisitkun, Prapaporn, Chindamporn, Ariya, Leelahavanichkul, Asada
• Format: Journal Article
• Language: English
• Published: Seoul The Microbiological Society of Korea 2019; Springer Nature B.V; 한국미생물학회
• Subjects: Animal models; Autoimmune diseases; Biomedical and Life Sciences; Cell activation; Creatinine; Cryptococcosis; Cryptococcus neoformans; Cytokines; Fungal infections; Genetic disorders; Genomics and Molecular Biology; Helper cells; Heterogeneity; Life Sciences; Lupus; Lupus nephritis; Macrophages; Microbial Genetics; Microbiology; Nephritis; Pathogenesis; Peritoneum; Phagocytosis; Pristane; Proteinuria; Serum; Spleen; γ-Interferon; 생물학; FcGRIIb deficient mice; susceptibility; murine model; pristane model; lupus; Cryptococcus neoformans
• ISSN: 1225-8873; 1976-3794
• DOI: 10.1007/s12275-019-8311-8

The severity of cryptococcosis in lupus from varying genetic-backgrounds might be different due to the heterogeneity of lupus-pathogenesis. This study explored cryptococcosis in lupus mouse models of pristane-induction (normal genetic-background) and FcGRIIb deficiency (genetic defect). Because the severity of lupus nephritis, as determined by proteinuria and serum creatinine, between pristane and FcGRIIb-/- mice were similar at 6-month-old,
Cryptococcus neoformans
was intravenously administered in 6-month-old mice and were age-matched with wild-type. Indeed, the cryptococcosis disease severity, as evaluated by mortality rate, internal-organ fungal burdens and serum cytokines, between pristane and FcGRIIb-/- mice was not different. However, the severity of cryptococcosis in wild-type was less severe than the lupus mice. On the other hand, phagocytosis activity of peritoneal macrophages from lupus mice (pristane and FcGRIIb-/-) was more predominant than the wild-type without the difference in macrophage killing-activity among these groups. In addition, the number of active T helper cells (Th-cell) in the spleen, including Th-cells with intracellular IFN-γ, from lupus mice (pristane and FcGRIIb-/-) was higher than wildtype. Moreover, these active Th-cells were even higher after 2 weeks of cryptococcal infection. These data support enhanced macrophage activation through prominent Th-cells in both lupus models. In conclusion, an increased susceptibility of cryptococcosis in both lupus models was independent to genetic background. This might due to Th-cell enhanced macrophage phagocytosis with the interference of macrophage killing activity from Cryptococcal immune-evasion properties.